scholarly journals EPCT-13. SINGLE INSTITUTION RETROSPECTIVE ANALYSIS OF TUMOR MUTATIONAL BURDEN AND SURVIVAL IN PEDIATRIC BRAIN TUMORS

2021 ◽  
Vol 23 (Supplement_1) ◽  
pp. i49-i49
Author(s):  
Rose Parisi ◽  
Roshal Patel ◽  
Lauren Weintraub
Keyword(s):  
Retrospective Analysis ◽  
Medical Center ◽  
Braf V600e ◽  
Cns Tumors ◽  
Driver Mutations ◽  
Low Grade ◽  
High Grade ◽  
Mutational Burden ◽  
Tumor Mutational Burden

Abstract Tumor mutational burden (TMB) has been studied across numerous cancer types as a means of risk stratification. To examine the prognostic relevance of TMB to pediatric central nervous system (CNS) tumors, we conducted a retrospective analysis of patients at Albany Medical Center diagnosed from 2012 to present. Patients were <21 at diagnosis, had a primary CNS tumor and available genomic data. Forty-seven patients were included – 22 low-grade gliomas, 10 high-grade gliomas, 5 medulloblastomas, 3 ependymomas, 2 choroid plexus carcinomas, and 5 other CNS tumors, with a median follow up of 36 months, median age at diagnosis 10 (1–19), and 47% female. Median TMB was 1 mutation per megabase (mut/mb); range 0–6. Nine patients did not have available TMB data. Twenty-seven patients had driver mutations and other alterations implicated in cancer development including, including BRAF-KIAA1549 fusion (n=6), NF1 loss (n=5), FGFR1 amplification (n=4), TP53 inactivation (n=4), BRAF V600E mutation (n=3), and H3F3A K28M mutation (n=3). Patients with low TMB (<3 muts/mb; n=24) versus high TMB (≥3 muts/mb; n=14) had a survival of 87% versus 71%, respectively, at last follow-up. Of note, all but one patient in the low TMB cohort had localized disease at diagnosis versus three in the high TMB cohort. High TMB was more prevalent in high- (45%, 9/20) versus low-grade histologies (22%, 4/18). Patients with BRAF alterations had LGGs and low TMB (0–1 muts/mb) with all patients surviving at last follow up. Of the eight deaths observed (median 18 months from diagnosis) TMB was high in 4, low in 3, and unknown in 1; all had high-grade histology. Although limited, our data suggests higher TMB may be associated with worse outcome. This analysis will be expanded via a multi-institutional review of TMB and genomic alterations in pediatric CNS patients to better identify high-risk patients requiring alternative treatment strategies.

scholarly journals LINC-42. EPIDEMIOLOGICAL OVERVIEW OF CHILDHOOD CNS TUMORS IN THE NEUROSURGICAL UNIT IN YEREVAN, ARMENIA

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii386-iii386
Author(s):  
Nune Karapetyan ◽  
Samvel Danielyan ◽  
Gevorg Tamamyan ◽  
Armen Tananyan ◽  
Liana Safaryan ◽  
...  
Keyword(s):  
Medical Center ◽  
Survival Rates ◽  
Developed Countries ◽  
Cns Tumors ◽  
Malignant Neoplasms ◽  
Low Grade ◽  
Embryonal Tumors ◽  
Low Grade Gliomas ◽  
Neurosurgical Treatment

Abstract BACKGROUND Central nervous system (CNS) tumors are the second most common malignant neoplasms among children worldwide. The current paper aims to analyze the situation in pediatric neuro-oncology in Armenia from the neurosurgical perspective. METHODS We have collected data of pediatric patients with CNS tumors treated in the Neurosurgery department of “Surb Astvasamayr” Medical Center from 01.01.2010 till 01.12.2019. Incidence by gender, age at diagnosis, and histopathology results were calculated. Survival rates were calculated based on the follow-up results performed until 30.12.2019. RESULTS Hospital-based data showed that during the previous 10 years 47 patients with CNS tumors received neurosurgical treatment in the unit, among them 66% were females. 38.3%, 31.9% and 29.8% of diagnosed patients were aged 0–4, 5–9, and 10–18 respectively. In 41 cases, the disease was not disseminated at diagnosis. The most common observed malignancies were low-grade gliomas (21.3%) and embryonal tumors (19.1%), followed by high-grade gliomas (14.9%) and ependymal tumors (8.5%). Follow-up information only for 33 patients is available. From them, 14 are dead and 19 alive. Survival rates in most common groups were 62.5%, 80%, 50%, and 50% respectively. The median follow-up time was 18 months (range 1–113 months). CONCLUSION Similar to the data reported in the literature, low-grade gliomas, and embryonal tumors are the most frequent pediatric CNS tumors in Armenia. On the other hand, the pediatric CNS tumor survival rates are lower compared to those reported in developed countries.

Mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs) of gastrointestinal (GI) tract: A single institution experience.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 633-633
Author(s):  
Manik A. Amin ◽  
Nikolaos Trikalinos
Keyword(s):  
Surgical Resection ◽  
Poor Prognosis ◽  
Braf V600e ◽  
Low Grade ◽  
Sequencing Analysis ◽  
High Grade ◽  
Gi Tract ◽  
Intermediate Grade ◽  
Disease Free

633 Background: MiNENs are heterogeneous group of rare tumors and represent less than 1% of all GI malignancies. These are pathologically classifiable according to neuroendocrine component into low grade, intermediate grade and high grade MiNENs but and managed based upon non-neuroendocrine component rather than true NENs. They have poor prognosis and less is known about treatment options. Methods: We identified 34 cases of MiNENs from 1/1/2000 to 1/1/2018 from Siteman Cancer Registry Database at Siteman Cancer Center, Washington University, St. Louis. Treatment and follow up information was obtained from medical charts of patients. Results: Of 34 identified cases of MiNENs, our database showed equal distribution of MiNENs in male and female patients (N = 17 each). Site of origin included appendix (N = 14), colon (N = 10), esophageal (N = 2), stomach (N = 3), rectum (N = 3), small intestine (N = 1) and ampulla of Vater (N = 1) locations. Histology was high grade (N = 22), intermediate grade (N = 8), low grade (N = 3) and unknown (1). Twenty nine (85%) underwent surgical resection with curative intent and 13 (40%) patients were disease free at five years of follow up. Disease was localized in 15 patients (44%) and distant metastasis were reported in 13 patients (40%). Ten out of 15 patient with localized disease were disease free with combined modality therapy of surgery and chemotherapy. Most common chemotherapy regimen used in the metastatic setting was FOLFOX (11), 5FU/capecitabine (3), and carboplatin plus etoposide (5). Next generation sequencing analysis was available on limited patients which showed MMR proficient (3), MMR deficiency (1), BRAF V600E mutation (1) and KRAS wild type (1). Conclusions: MiNENs of GI tract are rare and aggressive tumors and represent a distinct entity. Surgical resection whenever possible offers curative option. Our database of GI MiNENs showed efficacy with commonly used GI chemotherapy regimens. Patients with low grade tumor histology had better survival as compared to moderately and poorly differentiated tumors. Genomic testing through NGS would be recommended for personalized treatment decisions given poor prognosis in these patients.

Gender and Race As Prognostic Factors In Patients Treated With Rituximab For B-Cell Non-Hodgkin Lymphoma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3053-3053
Author(s):  
Mendel Goldfinger ◽  
Santiago Aparo ◽  
Krishna Gundabolu ◽  
Stefan K Barta
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Medical Center ◽  
Multivariate Model ◽  
Low Grade ◽  
High Grade ◽  
Final Multivariate Model ◽  
Non Hodgkin Lymphoma ◽  
Montefiore Medical

Abstract Introduction The International Prognostic Index (IPI) and the age-adjusted IPI (aaIPI) are the most commonly used tools to predict outcomes in patients with Non-Hodgkin Lymphoma (NHL). The IPI does not take into account sex or race. In the pre-rituximab era, sex was found to be a strong predictor of poor prognosis in low-grade lymphomas. While there is emerging evidence that female sex is associated with better survival in patients with diffuse large B-cell lymphoma (DLBCL) treated with R-CHOP, much less is known about the prognostic impact of race. We retrospectively assessed the impact of sex and race on overall survival in patients with indolent and aggressive NHL treated at any stage with rituximab at our institution. Methods We retrospectively identified all patients >/=18 years who were diagnosed with B-cell NHL (except SLL/CLL and Burkitt lymphoma) between 1/1/2000 and 12/31/2010 and received rituximab at any stage as part of their therapy at the Montefiore Medical Center. We collected data on histology, age (<60 vs. >/=60), date of diagnosis, date and status at last follow-up, and stage from the MECCC Cancer registry, and we obtained data on the Charlson Comorbidity Index (CCI) from Clinical Looking Glass® (CLG), an interactive software application developed at Montefiore Medical Center which integrates clinical and administrative datasets. The histological subtypes DLBCL and grade 3 follicular lymphoma (FL) were classified as “high-grade lymphoma” (HGL), while other types of lymphoma were termed “low-grade lymphoma” (LGL; these included marginal zone lymphoma, mantle cell lymphoma, grade 1 & 2 FL, and malignant lymphoma NOS). Self-reported race was classified as White, Black, Hispanic or “Other”. Only <2% of the patients were of “Other” racial background and therefore excluded from this analysis. The primary outcome was overall survival (OS) calculated as time from diagnosis to time of death. We used the Kaplan-Meier (KM) method to describe OS for race and sex and the log-rank test to test for significance (p<0.05). We used a Cox proportional hazard (CPH) model to assess the association of variables with OS. Except for age, race and sex, variables that were not significantly associated with OS (i.e. p-value>0.10 in the multivariate model) were excluded from the final model (backward elimination). Results 353 patients were included in the analysis. Median follow-up for all patients was 37.3 months (range 0.03-202.40). Baseline characteristics between male and females were similar with the exception of age at diagnosis and histology (see Table 1). On univariate analysis there was no OS difference between male and female patients (p=0.13), while race was associated with significant differences in OS (p=0.04; see Fig. 1). In the multivariate model, only stage >/=3 was associated with worse survival (Hazard Ratio [HR] 2.78, 95% CI 1.62-4.77; p<0.0001), but there was no significant association with OS for type of lymphoma (HGL vs. LGL) or the CCI (low vs. high score) and these 2 variables were therefore eliminated from the final multivariate model. In the final multivariate model, female sex was associated with a 37% reduction in the risk of death (HR 0.63; 95%CI 0.40-0.98; p=0.04), while race was no longer associated with OS (Hispanic vs. White: HR 0.76, 95%CI 0.41-1.40, p=0.38; Black vs. White: HR 0.66, 95%CI 0.40-1.10; p=0.11; Black vs. Hispanic: HR 1.15; 95% CI 0.63-2.08, p=0.65). Conclusions Female patients treated at any stage with rituximab for high-grade and low-grade B-cell NHL at our institution experienced longer OS. However, we observed no racial disparity in survival in our analysis. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Oral Abstract

2016 ◽  
Author(s):  
Dharma Ram
Keyword(s):  
Survival Data ◽  
Eligible Patient ◽  
Stage Iv ◽  
Endometrial Stromal Sarcoma ◽  
Uterine Sarcoma ◽  
Low Grade ◽  
Uterine Leiomyosarcoma ◽  
High Grade ◽  
Lost To Follow Up

Introduction: Uterine sarcoma accounts for nearly 3% of all uterine malignancies. They have 4 major pathology includes endometrial stromal sarcoma high grade, ESS low grade, uterine leiomyosarcoma (uLMS) and undifferentiated uterine sarcoma (UUS). Recent WHO classification 2014, recognizes low grade ESS and high grade ESS as distinct entity. They differ from endometrial carcinoma in their aggressive nature and poor prognosis. We review our database and found total 44 eligible patient treated at our institute. Materials and Methods: Its retrospective analysis of computer based database of our institute from January 2009 to December 2015. We analyzed demographic, pathological, treatment and survival data. Results: Total 44 patient treated for uterine sarcoma at our institute. Among these 16 were operated at our institute during study period. Here we reporting results of operated patients at our institute. The histological diagnosis LMS (5/16), ESS-L (4/16), MMMT (3/16), UUS (3/16) and ESS-H (1/16). Stage distribution was stage I, (6/16) stage II, (5/16) stage III, (3/16) stage IV, (0/16) and unknown stage (2/16). Two patients underwent completion surgery for outside myomectomy. The adjuvant treatment was CT in 3/16, CT with RT in 7/16, HT in 4/16 and one lost to follow up with one was put on observation. Median follow up is 30 month with 14 patients alive and one lost to follow up. At last follow up 4 patients alive with metastatic disease and 10 patients alive with no evidence of disease. Conclusion: Uterine sarcoma are uncommon disease with

Abstract CT025: Dabrafenib plus trametinib in BRAF V600E-mutant high-grade (HGG) and low-grade glioma (LGG)

2021 ◽  
Author(s):  
Vivek Subbiah ◽  
Alexander Stein ◽  
Martin van den Bent ◽  
Antje Wick ◽  
Filip Y. de Vos ◽  
...  
Keyword(s):  
Low Grade Glioma ◽  
Braf V600e ◽  
Low Grade ◽  
High Grade

scholarly journals Genetic Abnormalities, Clonal Evolution, and Cancer Stem Cells of Brain Tumors

2018 ◽  
Vol 6 (4) ◽  
pp. 85 ◽  
Author(s):  
Ugo Testa ◽  
Germana Castelli ◽  
Elvira Pelosi
Keyword(s):  
Brain Tumors ◽  
Clonal Evolution ◽  
Pediatric Brain Tumors ◽  
Genetic Alterations ◽  
World Health ◽  
Driver Mutations ◽  
Low Grade ◽  
High Grade ◽  
Genetic Profiling ◽  
Health Organization

Brain tumors are highly heterogeneous and have been classified by the World Health Organization in various histological and molecular subtypes. Gliomas have been classified as ranging from low-grade astrocytomas and oligodendrogliomas to high-grade astrocytomas or glioblastomas. These tumors are characterized by a peculiar pattern of genetic alterations. Pediatric high-grade gliomas are histologically indistinguishable from adult glioblastomas, but they are considered distinct from adult glioblastomas because they possess a different spectrum of driver mutations (genes encoding histones H3.3 and H3.1). Medulloblastomas, the most frequent pediatric brain tumors, are considered to be of embryonic derivation and are currently subdivided into distinct subgroups depending on histological features and genetic profiling. There is emerging evidence that brain tumors are maintained by a special neural or glial stem cell-like population that self-renews and gives rise to differentiated progeny. In many instances, the prognosis of the majority of brain tumors remains negative and there is hope that the new acquisition of information on the molecular and cellular bases of these tumors will be translated in the development of new, more active treatments.

scholarly journals Validation of a clinicopathological score for the prediction of post-surgical evolution of pituitary adenoma: retrospective analysis on 566 patients from a tertiary care centre

2019 ◽  
Vol 180 (2) ◽  
pp. 127-134 ◽  
Author(s):  
S Asioli ◽  
A Righi ◽  
M Iommi ◽  
C Baldovini ◽  
F Ambrosi ◽  
...  
Keyword(s):  
Pituitary Adenomas ◽  
Proliferative Activity ◽  
Disease Free Survival ◽  
Low Grade ◽  
High Grade ◽  
Tumour Type ◽  
Disease Evolution ◽  
Free Survival ◽  
Disease Free

Objective and design A clinicopathological score has been proposed by Trouillas et al. to predict the evolution of pituitary adenomas. Aim of our study was to perform an independent external validation of this score and identify other potential predictor of post-surgical outcome. Methods The study sample included 566 patients with pituitary adenomas, specifically 253 FSH/LH-secreting, 147 GH-secreting, 85 PRL-secreting, 72 ACTH-secreting and 9 TSH-secreting tumours with at least 3-year post-surgical follow-up. Results In 437 cases, pituitary adenomas were non-invasive, with low (grade 1a: 378 cases) or high (grade 1b: 59 cases) proliferative activity. In 129 cases, tumours were invasive, with low (grade 2a: 87 cases) or high (grade 2b: 42 cases) proliferative activity. During the follow-up (mean: 5.8 years), 60 patients developed disease recurrence or progression, with a total of 130 patients with pituitary disease at last follow-up. Univariate analysis demonstrated a significantly higher risk of disease persistence and recurrence/progression in patients with PRL-, ACTH- and FSH/LH-secreting tumours as compared to those with somatotroph tumours, and in those with high proliferative activity (grade 1b and 2b) or >1 cm diameter. Multivariate analysis confirmed tumour type and grade to be independent predictors of disease-free-survival. Tumour invasion, Ki-67 and tumour type were the only independent prognostic factors of disease-free survival. Conclusions Our data confirmed the validity of Trouillas’ score, being tumour type and grade independent predictors of disease evolution. Therefore, we recommend to always consider both features, together with tumour histological subtype, in the clinical setting to early identify patients at higher risk of recurrence.

scholarly journals Fewer actionable mutations but higher tumor mutational burden characterizes NSCLC in black patients at an urban academic medical center

Oncotarget ◽  
2019 ◽  
Vol 10 (56) ◽  
pp. 5817-5823 ◽  
Author(s):  
Noura J. Choudhury ◽  
Mansooreh Eghtesad ◽  
Sabah Kadri ◽  
John Cursio ◽  
Lauren Ritterhouse ◽  
...  
Keyword(s):  
Medical Center ◽  
Academic Medical Center ◽  
Mutational Burden ◽  
Academic Medical ◽  
Black Patients ◽  
Tumor Mutational Burden

Endoscopic Surveillance Practice for Barrett's Oesophagus in Scotland and Early Experience in Implementing Local Guidelines

2003 ◽  
Vol 48 (2) ◽  
pp. 43-45 ◽  
Author(s):  
E F Shen ◽  
S Gladstone ◽  
G Milne ◽  
S Paterson-Brown ◽  
I D Penman
Keyword(s):  
Early Experience ◽  
High Grade Dysplasia ◽  
Low Grade ◽  
High Grade ◽  
Wide Variability ◽  
Low Grade Dysplasia ◽  
Surveillance Practice ◽  
Four Quadrant ◽  
The Impact

Management of columnar lined oesophagus (CLO; Barrett s oesophagus) is controversial. We prospectively audited surveillance practices in Scotland and prospectively assessed the impact of introducing local guidelines for Barrett s surveillance in Edinburgh. Most respondents were gastroenterologists. The majority take random, not four quadrant, biopsies from the CLO. In Edinburgh during 2000, 80 patients underwent surveillance. The guideline protocol was not followed in 30 (37.5%) patients. Follow up of patients without dysplasia generally conformed to the guidelines. Follow up of patients with low grade dysplasia was highly variable while management of those with high grade dysplasia followed the guidelines. Overall we found a wide variability in the management and surveillance of CLO. Early experience suggests that implementation of guidelines is helpful but there is still variation in practice.

Survivorship After Meniscal Allograft Transplantation According to Articular Cartilage Status

2017 ◽  
Vol 45 (5) ◽  
pp. 1095-1101 ◽  
Author(s):  
Bum-Sik Lee ◽  
Seong-Il Bin ◽  
Jong-Min Kim ◽  
Won-Kyeong Kim ◽  
Jun Weon Choi
Keyword(s):  
Articular Cartilage ◽  
Graft Survival ◽  
Arthroscopic Surgery ◽  
Survival Rates ◽  
Low Grade ◽  
High Grade ◽  
Meniscal Allograft ◽  
Chondral Damage ◽  
Relative Indication

Background: Clinical outcomes after meniscal allograft transplantation (MAT) in arthritic knees are unclear, and objective estimates of graft survival according to the articular cartilage status have not been performed. Hypothesis: MAT should provide clinical benefits in knees with high-grade cartilage damage, but their graft survivorship should be inferior to that in knees with low-grade chondral degeneration after MAT. Study Design: Cohort study; Level of evidence, 3. Methods: The records of 222 consecutive patients who underwent primary MAT were reviewed to compare clinical outcomes and graft survivorship. The patients were grouped according to the degree and location of articular cartilage degeneration: low-grade chondral lesions (International Cartilage Repair Society [ICRS] grade ≤2) on both the femoral and tibial sides (ideal indication), high-grade lesions (ICRS grade 3 or 4) on either the femoral or tibial side (relative indication), and high-grade lesions on both sides (salvage indication). Kaplan-Meier survival analysis with the log-rank test was performed to compare the clinical survival rates and graft survival rates between the groups. A Lysholm score of <65 was considered a clinical failure, and graft failure was defined as a meniscal tear or meniscectomy of greater than one-third of the allograft, objectively evaluated by magnetic resonance imaging (MRI) and second-look arthroscopic surgery. Results: The mean (±SD) Lysholm score significantly improved from 63.1 ± 15.1 preoperatively to 85.1 ± 14.3 at the latest follow-up of a mean 44.6 ± 19.7 months ( P < .001). However, the postoperative scores were not significantly different between the 3 groups (85.7 ± 14.2 for ideal indication, 84.7 ± 17.0 for relative indication, and 84.7 ± 14.2 for salvage indication; P = .877). On MRI at the latest follow-up of a mean 23.0 ± 19.9 months and second-look arthroscopic surgery of a mean 19.3 ± 20.7 months, there were 25 (11.3%) failed MAT procedures (4 medial, 21 lateral); of these, 5 lateral MAT procedures (2.3%) went on to allograft removal. Clinical survival rates were not significantly different between the groups ( P = .256). However, on objective evaluation, the estimated cumulative graft survival rate at 5 years in the salvage indication group (62.2% [95% CI, 41.6-82.8]) was significantly lower than that in the other 2 groups (ideal indication: 93.8% [95% CI, 88.5-99.1]; relative indication: 90.9% [95% CI, 81.1-100.0]) ( P = .006). Conclusion: Our findings showed that MAT was an effective symptomatic treatment in knees with advanced bipolar chondral lesions. However, better graft survival can be expected when articular cartilage is intact or if chondral damage is limited to a unipolar lesion. MAT should be considered before the progression of chondral damage to a bipolar lesion for better graft survivorship and should be performed cautiously in arthritic knees.

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